1. Field of the Invention
Foot-and-mouth disease virus (FMDV) is responsible for one of the most devastating and contagious diseases in cattle and other cloven-hooved animals, affecting over 100,000 animals a year and resulting in significant economic loss. The disease occurs in many areas of the world outside the United States where vaccination programs have been largely effective. There are risks associated with the vaccines currently in use, however, and at present FMDV vaccines cannot be produced in the United States despite the continued threat of the introduction of this agent into the country. It is feared that the virus used to make vaccines could escape from containment and cause disease. Moreover, the failure to completely inactivate the virus during vaccine preparation has led to accidental outbreaks of infection. In addition, there is considerable antigenic variability among the various serotypes, thus some viruses may not be recognized by the vaccinated animals. Furthermore, frequent revaccination has been required in order to maintain protective immunity utilizing conventional vaccines containing virus attenuated by chemical inactivation (Bachrach, H. L. 1968. Annu. Rev. Microbiol. vol. 22, pp. 201-244). There is thus a strong incentive to develop an effective vaccine which eliminates the threat of infection due to the accidental outbreaks associated with vaccine production and administration. This invention relates to a new and safer vaccine against FMDV which provides effective protection but is not infectious, and thus does not present the risk of causing accidental infections.
2. Description of the Prior Art
In an effort to overcome the deficiencies of conventional virus vaccines, synthetic vaccines have been investigated. Identification of a flexible loop exposed on the virus surface as the main antigenic site of FMDV (site A) prompted the investigation of the use of various peptide fragments within site A to stimulate immunological responses. For example, the conserved tripeptide Arg-Gly-Asp (RGD) was evaluated for its ability to stimulate the production of neutralizing antibodies in rabbits or guinea pigs (Novella et al. 1993. FEBS Letters. vol. 330, no. 3, pp. 253-259).
Attempts to produce attenuated virus vaccines by genetic engineering were also carried out. Rieder et al. (1993. J. Virol. vol. 67, no. 9, pp. 5139-5145, herein incorporated by reference), for example, evaluated the role of the poly(C) tract found at the 5' end of the FMDV genome. Cardioviruses having shorter-than-natural poly(C) tracts had been shown to be dramatically attenuated; however, the poly(C) tract length of FMDV showed no effect on virulence when tested in mice.
Thus, the search for an improved vaccine has continued.